Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Human Genetics, |
RCV000659299 | SCV000781107 | pathogenic | CHARGE syndrome | 2016-11-01 | criteria provided, single submitter | clinical testing | |
DASA | RCV000659299 | SCV002073787 | likely pathogenic | CHARGE syndrome | 2022-02-05 | criteria provided, single submitter | clinical testing | This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (Clinvar ID: 547193; PMID: 29178447; 29300383) - PS4. This variant is not present in population databases (rs1554602588; gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. In summary, the currently available evidence indicates that the variant is likely pathogenic. |
New York Genome Center | RCV000659299 | SCV005044157 | pathogenic | CHARGE syndrome | 2022-10-26 | criteria provided, single submitter | clinical testing | The de novo c.5210+3A>G variant identified in the CHD7 gene has previously been reported in four individuals meeting clinical criteria for CHARGE syndrome [PMID: 21554267, 29178447, 35047002] and it has been deposited in ClinVar [ClinVar ID: 547193] as Pathogenic/Likely Pathogenic. This variant is absent from population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8, All of Us), suggesting it is not a common benign variant in the populations represented in those databases. The c.5210+3A>G variant is located in the donor splice region of exon 23 of this 37-exon gene and is predicted to affect mRNA splicing (Splice AI = 0.45(acceptor loss) and 0.51 (donor loss)) which might result in loss-of-function via exon skipping or intron retention; however, there are no functional studies to support or refute this prediction. Based on available evidence this de novo c.5210+3A>G variant identified in CHD7 is classified here as Pathogenic. |